Methicillin-Sensitive Staphylococcus aureus (MSSA) refers to all of the antibiotic-sensitive strains of Staphylococcus aureus. Accordingly, MSSA refers to the common type of Staphylococcus aureus (Staph. aureus) that causes most Staph. aureus infections and that can be treated with penicillin-type antibiotics. By contrast, Methicillin-Resistant Staphylococcus aureus (MRSA) refers to a subgroup of Staph. aureus that is resistant to a range of penicillin antibiotics, including Methicillin. MRSA first appeared in 1961 soon after the introduction of the antibiotic Methicillin. Both MSSA and MRSA have virulence/pathogenicity factors that allow for adhesion to cell surfaces and immune evasion/killing. Studies conducted comparing the pathogenicity of MRSA and MSSA have resulted in some conflicting data. What is clear, however, is that perhaps the most significant difference between MRSA and MSSA is MRSA's resistance to Methicillin. MRSA's resistance arises from the presence of the penicillin-binding protein 2a (PBP2a) protein on the surface of the bacteria. PBP2a protein is encoded by the mecA gene.
Staph. aureus infections, including MRSA (Methicillin Resistant Staph. aureus), occur most frequently among persons in hospitals and other healthcare facilities, such as for example nursing homes and dialysis centers. These healthcare-associated Staph infections include, among others, surgical wound infections, urinary tract infections, bloodstream infections, and pneumonia. MRSA can cause skin infections that may look like a pimple or boil and can be red, swollen, painful, or have pus or other drainage. More serious infections may cause pneumonia, bloodstream infections, or surgical wound⋅infections. The most recent estimate of the number of people developing a serious MRSA infection (i.e., invasive) is about 94,360 patients. Approximately 18,650 persons died during a hospital stay as the result of a serious MRSA infection (˜20% mortality).
Attempts at developing DNA vaccines against MRSA using plasmids with nucleic acid sequences that encode PBP2a or fragments thereof have bee reported. Ohwada A, et al. DNA vaccination by mecA sequence evokes an antibacterial immune response against methicillin-resistant Staphylococcus aureus, J Antimicrob Chemother. 1999 December; 44(6):767-74, describes the intramuscular injection of a DNA plasmid that comprises the PBP2a protein-encoding mecA gene cloned from the N315 MRSA isolate. Roth D M, et al. Evaluation of the humoral immune response in BALB/c mice immunized with a naked DNA vaccine anti-methicillin-resistant Staphylococcus aureus, Genet Mol Res. 2006 Aug. 31; 5(3):503-12, and Senna J P, et al. Protective immune response against methicillin resistant Staphylococcus aureus in a murine model using a DNA vaccine approach. Vaccine. 2003 Jun. 2; 21(19-20):2661-6 report intramuscular injection was used to deliver a DNA plasmid that comprised only a 249 base pair fragment of the mecA gene cloned from the HSP-03 clinical MRSA isolate.
There remains a need for a vaccine useful to prevent or treat MRSA infections. There remains a need for nucleotide sequences that encode MRSA PBP2a or fragments thereof which can be expressed in high levels when incorporated into a vaccine such that effective immune responses against MRSA Staph. aureus that expresses PBP2a. are induced, thereby providing therapeutic effects in infected individuals or long-term protection against MRSA infection.